Resistance to Recombinant Human Granulocyte Colony-Stimulating Factor in Neonatal Alloimmune Neutropenia Associated With Anti-Human Neutrophil Antigen-2a (NB1) Antibodies

Abstract

ABSTRACT. Neonatal alloimmune neutropenia is the neutrophil counterpart of the erythrocyte disorder of hemolytic disease of the newborn. Fetal neutrophil antigens, which are inherited from the father but foreign to the pregnant mother, provoke the formation of maternal antibodies, which, on transplacental passage, cause fetal/ neonatal neutropenia. Because infants with this disorder are at a higher risk of infection, recombinant hematopoietic growth factors, such as recombinant human granulocyte colony-stimulating factor, have been tried, with generally good results, to treat those with severe and prolonged neutropenia. We report a neonate who had neonatal alloimmune neutropenia associated with antibodies directed against human neutrophil antigen-2a (NB1) and initially failed to respond to even very high doses of recombinant human granulocyte colony-stimulating factor but eventually had a therapeutic response.

Neonatal Alloimmune Neutropenia

“…Treatment with G-CSF is highly effective in increasing neutrophil numbers within days in a majority of cases and can be considered especially for neonates suffering from severe infections [60,61,62]. One should keep in mind that resistance to G-CSF in NAIN associated with anti-HNA-2 antibodies, possibly due to a G-CSF-induced increase of HNA-2 expression on the neutrophils, has been described [63,64,65]. Despite the stimulated production of neutrophils, controversial results on the benefit of G-CSF in terms of infection-free survival have been published [66,67,68,69,70].…”

Neutropenia in the newborn

“…In an occasional patient, G-CSF therapy will not raise blood neutrophil counts. G-CSF doses may be increased in increments of 10 μg/kg at 7–14-day intervals if the ANC remains below 1000/μL (37, 69). Doses can be reduced or withheld once ANCs reach >5000/μL.…”

Disorders of the Fetomaternal Unit: Hematologic Manifestations in the Fetus and Neonate

“…Higher doses of rhG-CSF may be required in ANN due to anti-HNA-2a antibodies, which is associated with decreased neutrophil production in addition to peripheral destruction of neutrophils. 51 rhG-CSF is usually well-tolerated without adverse effects at the doses and duration of treatment needed for ANN. The mechanisms of action of rhG-CSF in ANN include increased neutrophil production, release of neutrophils from the post-mitotic storage pools in the marrow, and increased neutrophil survival.…”